The proposal is concerned with studies on glucocorticoid binding and on glucocorticoid-receptor complex interaction with the nucleus in murine and human corticoid-sensitive (CS) and -resistant (CR) leukemic lymphocytes. The objective is to investigate whether differences in nuclear glucocorticoid binding between CS and receptor (plus) CR lymphocytes are due to the receptor itself, to nuclear components, or to both, and to shed light on the nature of the determinants for nuclear binding in CS and CR cells. These aspects will be explored with whole cell and cell-free nuclear uptake systems, using probes that selectively interact with chromatin DNA, in conjunction with controlled DNase digestion of nuclei and controlled cleavage of receptors with proteases. Other studies will be directed towards developing a cell-free, functional assay for glucocorticoid receptor and towards identification of possible "abortive" glucocorticoid actions in CR lymphocytes.